Background: Some studies have investigated the association of GSTM1, GSTT1, GSTM3, and GSTP1polymorphisms with susceptibility to osteosarcoma; however, these studies results are inconsistent and inconclusive. Inorder to drive a more precise estimation, the present case-control study and meta-analysis was performed to investigateassociation of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with osteosarcoma. Methods: Eligible articleswere identified by a search of several electronic databases for the period up to May 5, 2018. Odds ratios were pooledusing either fixed-effects or random effects models. Results: Finally, a total of 24 case-control studies with 2,405osteosarcoma cases and 3,293 controls were included in the present meta-analysis. Overall, significantly increasedosteosarcoma risk was found when all studies were pooled into the meta-analysis of GSTT1 (Null vs. Present: OR= 1.24795% CI 1.020-1.524, P= 0.031) and GSTP1 polymorphism (B vs. A: OR= 8.899 95% CI 2.722-29.094, P≤0.001). Inthe stratified, significantly increased osteosarcoma risk was observed for GSTT1 polymorphism among Asians (Nullvs. Present: OR= 1.300 95% CI 1.034-1.635, P= 0.025), but not among Caucasians. Conclusions: This meta-analysisdemonstrated that GSTP1 and GSTT1 null genotype are associated with the risk of osteosarcoma. Future large welldesigned epidemiological studies are warranted to validate our results.